The cyclic nucleotide phosphodiesterases and the heat stable and non-dialyzable protein activators of phosphodiesterase are present in the following tissue culture cell lines: leukemia CEM, breast cancer MCF-7, human eye cancer #49, #57, Y-79, WERI and the rabbit eye cancer cell lines and also the rabbit eye cancer tissue directly removed from rabbits. All protein activators activate bovine brain cyclic nucleotide phosphodiesterase and the activations are Ca ions dependent. In the presence of Ca ions, the protein activator of CEM cell was more resistant to trypsin inactivation, presumably because of a Ca ions induced conformational change in protein activator to a more helical structure.